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Non-Hodgkin lymphoma classification and staging

This page presents information on non-Hodgkin lymphoma (NHL) classification and staging.

Classification of non-Hodgkin lymphoma

In the World Health Organisation (WHO) system, 1 non-Hodgkin lymphomas are classified as far as possible according to their normal counterparts in B or T lymphocyte lineage. In addition to its biological relevance, this system has direct clinical applicability and is becoming the accepted international standard.

An increasing number of cytogenetic and molecular abnormalities are now being identified in various subtypes of NHL. These abnormalities often result in the over-expression of oncogenes, or of anti-apoptotic genes. Although their clinical significance remains unclear, there is emerging evidence that some of these abnormalities may provide prognostic information, and that they may prove useful ‘tumour markers’ for monitoring the presence of residual disease (Table 5.1)

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Despite the complex nature of the classification system, many of the major subtypes of NHL can be grouped into low-, intermediate-, or high-grade categories, reflecting their clinical behaviour.

NHL Staging and Prognostic factors

Until recently, the Ann Arbor staging system, which is based entirely on anatomical extent of disease, was the major determinant of therapy in NHL. Although it remains an important factor in treatment decisions, it is now recognised that several other presenting features of the disease are important predictors of outcome.

The International Prognostic Index (IPI)2 was constructed to provide a predictive model for aggressive NHL, based on presenting features. Patients can be stratified into four risk groups according to their presenting characteristics.

A similar index has now been developed for risk stratification in follicular lymphoma. 3

In addition to the clinical and morphologic features of NHL, aspects of the immunophenotype, genotype and patterns of gene expression are emerging as carrying important prognostic information. For example the expression of Bcl-2 protein is known to carry an adverse prognostic significance in large B-cell NHL, whilst expression of germinal centre markers such as CD10 and Bcl-6 are favourable. 4

Such distinctions have been carried further in microarray-based analysis of gene expression, and the separation into germinal centre type versus activated B-cell type large cell lymphoma on this basis has been described as giving prognostic information independent of the normal clinical index. 5

Interestingly a similar analysis of gene expression in material from follicular lymphoma suggested that the presence of infiltrating immune cells rather than expression of genes by the lymphoma cells themselves gave the most accurate prognostic information, suggesting an important role for the host response. 6

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References for non-Hodgkin lymphoma classification and staging

1. Harris NL, Jaffe ES, Diebold J, et al. World Health Organization classification of neoplastic diseases of the hematopoietic and lymphoid tissues: report of the Clinical Advisory Committee meeting-Airlie House, Virginia, November 1997 J Clin Oncol 1999;17(12):3835-49.
2. A predictive model for aggressive non-Hodgkin's lymphoma. The International Non-Hodgkin's Lymphoma Prognostic Factors Project. N Engl J Med 1993;329(14):987-94.
3. Solal-Celigny P, Roy P, Colombat P, et al. Follicular lymphoma international prognostic index. Blood 2004;104(5):1258-65.
4. Barrans SL, Carter I, Owen RG, et al. Germinal center phenotype and bcl-2 expression combined with the International Prognostic Index improves patient risk stratification in diffuse large B-cell lymphoma. Blood 2002;99(4):1136-43.
5. Rosenwald A, Wright G, Chan WC, et al. The use of molecular profiling to predict survival after chemotherapy for diffuse large-B-cell lymphoma. N Engl J Med 2002;346(25):1937-47.
6. Dave SS, Wright G, Tan B, et al. Prediction of survival in follicular lymphoma based on molecular features of tumor-infiltrating immune cells. N Engl J Med 2004;351(21):2159-69.

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